Extended Data Fig. 10: A proposed model for the generation of mitophers in C. elegans spermatids.

During sperm development in male C. elegans, spermatids generate mitophers through plasma outward budding to export healthy mitochondria into the extracellular space to reduce mitochondrial quantity. During mitopherogenesis, the mitopher is released immediately upon the formation of the bud that contains one mitochondrion. The mitopher is a membrane-bound vesicle sized around 490–1,100 nm that is featured by its cargo, only one single mitochondrion, and the biogenesis via quick plasma membrane budding-off. In the testis, the extracellular protease signal triggers mitopherogenesis partially through SPE-8. Moreover, normal microfilaments dynamics are required for generating mitophers, and myosin VI negatively regulate mitopher generation. Mitopherogenesis represents a previously-unknown process to specifically export mitochondria out of cells, which is critical for modulating sperm mitochondrial quantity that may be important for producing motile male gametes. Created with BioRender.com.